Age-Related Differences in Adolescent Brain Microstructure: Initial Findings from National Consortium on Alcohol & Neurodevelopment in Adolescence
[email protected]♦ http://www.stanford.edu/~kpohl
Kilian M. Pohl, Ph.D. Center for Health Sciences, SRI International Department of Psychiatry & Behavioral Sciences, Stanford
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Financial Interest Disclosure Salary and Research Support
of Kilian M Pohl, Ph.D.
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Goal
Investigate Aging of the White Matter Microstructure in Adolescents
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Overview
• NCANDA Data Acquisition • DWI Specific Processing • Current Findings (N=671)
Data Acquisition
Monitoring brain development of 831 adolescence over a 5 year period across 5 sites
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NCANDA Collection Sites
created by N. Nichols
Sites collect: • Demographic Information • Clinical Data • Neuropsychological Test Scores • MRI
• Structural • Diffusion • Functional
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NCANDA – Informatics Platform
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Robustly and coherently fusing data across time, sites, and modalities
Diffusion Weighted Imaging
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White matter contains axons that group together to bundles connecting gray matter regions
Fibers restrict diffusion of water molecules
Diffusion Weighted Imaging
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Courtesy of Human Connectome Project
Ellipsoid represents diffusion direction at location
Measure the rate of diffusion within white matter
by varying gradient direction of scanner’s magnetic field
Diffusion Weighted Imaging
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Summarize diffusion via Fractional Anisotropy (FA)
FA=0 FA=0.8
Image
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Acquisition
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Acquire DWI of 831 subjects (12-22 years) on Siemens TIM TRIO and GE Discovery MR750: • Reverse:
2D Axial Spin Echo Echo-Planar - b=0/500, 6 directions (TR=10,000, TE=85, Thick=2.5, Loc=65, FOV=240, xy_matrix=96x96, Phase = A/P, Partial k-space (48/64), Acceleration=2, Resolution=2.5x2.5x2.5 mm, Fat Sat=on)
To correct for B0 field inhomogeneity spatial distortion
• Forward: 2D Axial Spin Echo Echo-Planar - b=0/1000, 60 directions (TR=10,000, TE=85, Thick=2.5, Loc=65, FOV=240, xy_matrix=96x96, Phase = A/P, Partial k-space (48/64), Acceleration=2, Resolution=2.5x2.5x2.5 mm, Fat Sat=on)
To compute FA Maps
Data Distribution and Archival
created by N. Nichols
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Archive and share data via local it infrastructure and the Cloud
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Overview
• NCANDA Data Acquisition • DWI Specific Processing • Current Findings (N=671)
Correct for Manufacture Differences
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Normalize FA accounting for scanner differences: • scan the same 3 human phantoms at all 5 sites • compute ratio of mean FA value across scanner type • apply ratio to FA maps
Smaller Variation
Tract-Based Spatial Statistics (TBSS)*
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* Smith et al. 2006
Compare FA maps via TBSS Skeleton
Case 01 Case 12
Case 13 Case N
Case 51
Case 43
Case 32
Case37
Tract-Based Spatial Statistics (TBSS)*
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* Smith et al. 2006
Compute Mean Skeleton
Case 01 Case 12
Case 13 Case N
Case 51
Case 43
Case 32
Case37
Tract-Based Spatial Statistics (TBSS)*
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* Smith et al. 2006
Compute Subject Specific Skeleton
Case 01 Case 12
Case 13 Case N
Case 51
Case 43
Case 32
Case37
Compute Mean Skeleton FA for ROI
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* Smith et al. 2006
ROIs are defined according to JHU DTI Atlas (Mori et al. 2005)
Case 01 Case 12
Case 13 Case N
Case 51
Case 43
Case 32
Case37
General Additive Model (GAM)
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For each ROI of the atlas regress a thin plate spline with 3 control points to the mean skeleton FA values of that region (meanFAROI) of the 671 subjects with the subject’s age being the predictor value and factors race, sex, and suptent supratentorium volume (svol): GAM[ meanFAROI ~ s(age, bs = "ts", k = 3) + race + sex + svol]
Picture
P –value computations
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Overview
• NCANDA Data Acquisition • DWI Specific Processing • Current Findings (N=671)
Global Skeleton
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Age (years)
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Global Skeleton
• Fiber organization peaks at 18.2 years • African-Americans have higher and
Asians have lower mean skeleton FA compared to Caucasians
Male Female
P value of findin
Commissural Fibers
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Genu
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Splenium
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Body
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Tapetum
Development of white matter fiber systems is ROI specific
PROJECTION FIBERS: Brainstem Tracts
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Pontine Crossing Fibers
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Superior Cerebellar Peduncle
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Middle Cerebellar Peduncle
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Cerebral Peduncle
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Inferior Cerebellar Peduncle
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PROJECTION FIBERS: Corticospinal Tracts (Part 1)
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Superior Corona Radiata
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Anterior Corona Radiata
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Posterior Corona Radiata
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Posterior Thalamic Radiation
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PROJECTION FIBERS: Corticospinal Tracts (Part 2)
Adj
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Age (years)
Corticospinal Tract
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Age (years)
Medial Lemniscus
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Anterior Internal Capsule
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Posterior Internal Capsule
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Retrosplenial Internal Capsule
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External Capsule
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Anterior Middle Cingulum
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Age (years)
Stria Terminalis
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Inferior Cingulum
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Fornix
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ASSOCIATION FIBERS: Limbic Tracts
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ASSOCIATION FIBERS: Fasciculi
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Adj
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Age (years)
Superior Longitudinal Fasciculus
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Superior Frontal Occipital Fasciculus
Adj
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Age (years)
Sagittal Striatum
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Age (years)
Uncinate Fasciculus
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Conclusion
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• Heterochronicity characterizes developmental patterns of white matter fiber systems in adolescence, e.g., commissural and selective projection systems reach peak fiber organization (assumed from FA) earlier than limbic association fibers.
• These patterns of age-related differences need confirmation with longitudinal examination.
• The continuing development of fiber bundles estimated from this cross-sectional analysis may render them vulnerable to environmental insult, including initiation of hazardous drinking.
Thank You
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This work was supported by the U.S. National Institute on Alcohol Abuse and Alcoholism with co-funding from the National Institute on Drug Abuse, the National Institute of Mental Health, and the National Institute of Child Health and Human Development [NCANDA grant numbers: AA021697, AA021695, AA021692, AA021696, AA021681, AA021690, AA021691
Nolan Nichols, Ph.D. Yong Zheng, Ph.D. Dongjin Kwon, Ph.D.
